AB, biochemical sciences, Princeton University。 MD/PhD, molecular biology, Washington University School of Medicine, St. Louis。 Dr. Littman is also a professor of pathology and microbiology at the Skirball Institute of Biomolecular Medicine of New York University School of Medicine. Memberships: National Academy of Sciences; Institute of Medicine; American Academy of Arts and Sciences; Association of American Physicians; American Academy of Microbiology。 Our laboratory investigates 1) the molecular events underlying T-lymphocyte differentiation and activation and 2) how the human immunodeficiency virus (HIV) enters target cells and causes systemic depletion of helper T cells. In both areas, we study the functions of T-cell surface molecules and their interactions with intracellular signal transducing components. During development, CD4 and CD8 glycoproteins are co-expressed on immature thymocytes (double-positive cells), which are then selected according to their ability to interact productively with host major histocompatibility complex (MHC) molecules expressed on thymic epithelium. Cells with T-cell receptors specific for MHC class I shut off CD4 and commit to becoming cytotoxic cells, while cells with T-cell receptors for MHC class II shut off CD8 and become helper cells. We use gene targeting and transgenic technology in mice to study how the double-positive cells commit to either of the two major T-lymphocyte lineages. In our studies with immunodeficiency viruses, we seek to understand how the interaction of viral envelope glycoproteins with CD4 and various chemokine receptors on the target cells results in membrane fusion and viral entry. We are also developing mouse model systems to determine how HIV infection causes loss of CD4+ helper T cells. In related studies, the functions of chemokine receptors in development and in inflammatory responses are being investigated.